Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia

Abstract BackgroundPreeclampsia is still the leading cause of morbidity and mortality in pregnancy, however there are no current effective therapeutic strategies. This has been impeded by poorly understood pathogeneses of preeclampsia and its multifactorial and heterogeneous nature. Two phenotypes of preeclampsia have been characterised based on the time of diagnosis, early-onset (EOPE, before 34 weeks’ of gestation) and late-onset (LOPE, from 34 weeks’ of gestation). However, the molecular differences between these two phenotypes are not fully elucidated. ObjectivesThis study aimed to facilitate better understanding of the mechanisms of pathogenesis of EOPE and LOPE, and identify specific biomarkers of preeclampsia.MethodsIn this study, we conducted an untargeted proteomic analyses of plasma samples from pregnant women with EOPE (n=17) and LOPE (n=11), and age, BMI-matched normotensive controls (n=18).ResultsIn total, there were 26 and 20 differentially abundant proteins between EOPE or LOPE, and normotensive controls, respectively. Only inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3) was differentially abundant and 11 proteins were commonly shared between EOPE and LOPE. A series of angiogenic proteins, including insulin-like growth factor-binding protein 4 (IGFBP4; EOPE: FDR =0.30 x 10-3 and LOPE: FDR =3.96 x 10-3) and histidine-rich glycoprotein (HRG), were significantly perturbed in both phenotypes (EOPE: FDR=7.8 x 10-3; LOPE: FDR =4.1 x 10-3). ConclusionsOverall, proteins associated with lipid metabolism were the key proteins perturbed in EOPE, however, ECM proteins had a more pronounced role in LOPE. The homeostasis-related pathway including platelet activation, signalling and aggregation were more perturbed in EOPE than LOPE.